Extension Study of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis

Phase 3

• Conditions: Idiopathic Pulmonary Fibrosis; Interstitial Lung Disease
• Interventions: Drug: Inhaled Treprostinil; Device: Treprostinil Ultrasonic Nebulizer

• Registration Number: NCT04905693
• Lead Sponsor: United Therapeutics

Brief Summary

Study RIN-PF-302 is designed to evaluate the long-term safety and tolerability of inhaled treprostinil in subjects with idiopathic pulmonary fibrosis.

Detailed Description

Study RIN-PF-302 is a Phase 3, multicenter, open-label extension (OLE) study for eligible subjects who completed Study RIN-PF-301 or Study RIN-PF-303 to evaluate the long-term safety and tolerability of inhaled treprostinil in subjects with idiopathic pulmonary fibrosis (IPF). Following OLE entry, subjects will return at Week 4, Week 12, and every 12 weeks thereafter for up to 6 years or until the subject prematurely discontinues study treatment due an adverse event (AE)/serious adverse event (SAE) or other reason, inhaled treprostinil becomes commercially available for IPF, or the study is discontinued by the Sponsor (whichever is sooner).

Efficacy assessments will include spirometry (forced expiratory volume in 1 second \[FEV1\] and forced vital capacity \[FVC\]), time to clinical worsening, time to first acute exacerbation of IPF, overall survival, King's Brief Interstitial Lung Disease (K-BILD) Questionnaire, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration, supplemental oxygen use, and diffusion capacity of lungs for carbon monoxide (DLCO). Safety assessments will include monitoring for the development of AEs/SAEs, vital signs, clinical laboratory parameters, and electrocardiogram (ECG) parameters. In addition, up to 24 eligible subjects may participate in a PK substudy to evaluate the systemic exposure of treprostinil after inhaled administration.

Study Timeline

• Study First Submitted: 2021-05-20
• Study First Submitted QC: 2021-05-25
• Study First Posted: 2021-05-28
• Study Start: 2022-09-06
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-24
• Last Update Posted: 2025-04-25
• Primary Completion: 2026-06
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 792

Inclusion Criteria

1. Subject gives voluntary informed consent to participate in the study.
2. The subject participated in Study RIN-PF-301 or Study RIN-PF-303 and remained on study drug and completed all scheduled study visits or was enrolled in Study RIN-PF-301 or Study RIN-PF-303 at the time that the study or study subject was discontinued by the Sponsor.
3. Women of childbearing potential must be non-pregnant (as confirmed by a urine pregnancy test at OLE Entry Visit and Baseline) and non-lactating, and will abstain from intercourse (when it is in line with their preferred and usual lifestyle) or use 2 medically acceptable, highly effective forms of contraception for the duration of the study, and at least 30 days after discontinuing study drug.
4. Males with a partner of childbearing potential must use a condom for the duration of treatment and for at least 48 hours after discontinuing study drug.
5. In the opinion of the Investigator, the subject is able to communicate effectively with study personnel, and is considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits.

Exclusion Criteria

1. Subject is pregnant or lactating.
2. In the opinion of the Investigator, enrollment in Study RIN-PF-302 would represent a risk to the subject's overall health.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Inhaled Treprostinil	Inhaled Treprostinil	Treprostinil inhalation solution (0.6 mg/mL) delivered via an ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath. Inhaled QID and titrated to a target of 15 breaths QID or until the subject reaches their maximum clinically tolerated dose.
Inhaled Treprostinil	Treprostinil Ultrasonic Nebulizer	Treprostinil inhalation solution (0.6 mg/mL) delivered via an ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath. Inhaled QID and titrated to a target of 15 breaths QID or until the subject reaches their maximum clinically tolerated dose.

Primary Outcome Measures

Name	Time	Method
Long-term safety and tolerability of inhaled treprostinil in subjects with IPF	Baseline to 6 years	Incidence of AEs and SAEs, incidence of abnormal clinical laboratory parameters, abnormal vital signs, and abnormal 12-lead ECGs

Trial Locations

Locations (168)

Community Health Network; 🇺🇸 Indianapolis, Indiana, United States

PulmonIx, LLC; 🇺🇸 Greensboro, North Carolina, United States

Hôpital Bretonneau; 🇫🇷 Tours, Indre-et-Loire, France

CHU Amiens-Picardie; 🇫🇷 Amiens, France

AP-HP - Hopital Avicenne; 🇫🇷 Bobigny, France

Hospices Civils De Lyon - Université Hospital of Lyon; 🇫🇷 Bron, France

AP-HP - Hôpital Européen Georges Pompidou; 🇫🇷 Paris, France

Hôptial Bichat; 🇫🇷 Paris, France

Centre Hospitalier Universitaire De Reims - Hôpital Maison Blanche; 🇫🇷 Reims, France

Hôpital Pontchaillou; 🇫🇷 Rennes, France

Sheba Medical Center - PPDS; 🇮🇱 Ramat Gan, Tel-Aviv, Israel

Lady Davis Carmel Medical Center; 🇮🇱 Haifa, Israel

Meir Medical Center; 🇮🇱 Kfar Saba, Israel

Rabin Medical Center - PPDS; 🇮🇱 Petah Tiqva, Israel

Tel Aviv Sourasky Medical Center - PPDS; 🇮🇱 Tel Aviv, Israel

Fondazione Policlinico Universitario A Gemelli-Rome; 🇮🇹 Roma, Lazio, Italy

Gruppo MultiMedica SpA - Ospedale San Giuseppe; 🇮🇹 Milan, Lombardia, Italy

Azienda ospedaliero-universitaria Senese; 🇮🇹 Siena, Toscana, Italy

Azienda Ospedaliero Universitaria delle Marche; 🇮🇹 Ancona, Italy

Presidio Ospedaliero GB Morgagni L Pierantoni; 🇮🇹 Forlì, Italy

Hospital General Universitario Gregorio Marañon; 🇪🇸 Madrid, Spain

Hospital Clinico San Carlos; 🇪🇸 Madrid, Spain

Hospital Clinico Universitario Virgen de La Arrixaca; 🇪🇸 Murcia, Spain

Hospital Universitario Marques de Valdecilla; 🇪🇸 Santander, Spain

Kaohsiung Medical University - Chung-Ho Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

E-DA hospital; 🇨🇳 Kaohsiung, Taiwan

CHU de Liège; 🇧🇪 Liège, Belgium

Emory University; 🇺🇸 Atlanta, Georgia, United States

The University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Clinical Trials Center of Middle Tennessee; 🇺🇸 Franklin, Arizona, United States

Banner University Medical Center-Phoenix; 🇺🇸 Phoenix, Arizona, United States

St. Joseph's Hospital and Medical Center - Norton Thoracic Institute; 🇺🇸 Phoenix, Arizona, United States

University of Arizona; 🇺🇸 Tucson, Arizona, United States

David Geffen School of Medicine at UCLA; 🇺🇸 Los Angeles, California, United States

NewportNativeMD, Inc; 🇺🇸 Newport Beach, California, United States

Palmtree Clinical Research, Inc.; 🇺🇸 Palm Springs, California, United States

UC Davis Health Medical Center; 🇺🇸 Sacramento, California, United States

Stanford University School of Medicine; 🇺🇸 Stanford, California, United States

National Jewish Health; 🇺🇸 Denver, Colorado, United States

University of Florida Health at Shands; 🇺🇸 Gainesville, Florida, United States

Ascension St. Vincent's; 🇺🇸 Jacksonville, Florida, United States

University of Florida; 🇺🇸 Jacksonville, Florida, United States

Mayo Clinic Florida; 🇺🇸 Jacksonville, Florida, United States

Pulmonary Disease Specialists, PA d/b/a PDS Research; 🇺🇸 Kissimmee, Florida, United States

Central Florida Pulmonary Group, PA; 🇺🇸 Orlando, Florida, United States

Coastal Pulmonary & Critical Care PLC; 🇺🇸 Saint Petersburg, Florida, United States

University of South Florida Health; 🇺🇸 Tampa, Florida, United States

Cleveland Clinic Florida; 🇺🇸 Weston, Florida, United States

Piedmont Healthcare Atlanta; 🇺🇸 Atlanta, Georgia, United States

Northwestern Memorial Hospital; 🇺🇸 Chicago, Illinois, United States

Loyola University Medical Center; 🇺🇸 Maywood, Illinois, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States

Norton Pulmonary Specialists; 🇺🇸 Louisville, Kentucky, United States

University of Louisville Healthcare Outpatient Center; 🇺🇸 Louisville, Kentucky, United States

Tulane University Medical Center; 🇺🇸 New Orleans, Louisiana, United States

LSU Health Science Center Shreveport; 🇺🇸 Shreveport, Louisiana, United States

Johns Hopkins Asthma and Allergy Center; 🇺🇸 Baltimore, Maryland, United States

Adventist Healthcare White Oak Medical Center; 🇺🇸 Silver Spring, Maryland, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Michigan Int Med Pulmonary and critical care; 🇺🇸 Ann Arbor, Michigan, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

Corewell Health William Beaumont Hospital; 🇺🇸 Royal Oak, Michigan, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Mayo Clinic, Division of Pulmonary and Critical Care Medicine; 🇺🇸 Rochester, Minnesota, United States

University Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States

The Lung Research Center, LLC; 🇺🇸 Chesterfield, Missouri, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Creighton University Clinical Research Office; 🇺🇸 Omaha, Nebraska, United States

University of New Mexico Health Sciences Center; 🇺🇸 Albuquerque, New Mexico, United States

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States

Northwell Health; 🇺🇸 New Hyde Park, New York, United States

University of Rochester Medical Center; 🇺🇸 Rochester, New York, United States

East Carolina University; 🇺🇸 Greenville, North Carolina, United States

Southeastern Research Center; 🇺🇸 Winston-Salem, North Carolina, United States

University of Cincinnati Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

The Ohio State University Wexner Medical Center; 🇺🇸 Columbus, Ohio, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

The Oregon Clinic; 🇺🇸 Portland, Oregon, United States

Penn State Milton S.Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

Hospital of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Thomas Jefferson,Hospital University; 🇺🇸 Philadelphia, Pennsylvania, United States

Temple University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Prisma Health Midlands; 🇺🇸 Columbia, South Carolina, United States

Clinical Research of Rock Hill; 🇺🇸 Rock Hill, South Carolina, United States

StatCare Pulmonary Consultants, PLLC; 🇺🇸 Knoxville, Tennessee, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Baylor University Medical Center; 🇺🇸 Dallas, Texas, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

The University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States

A & A Research Consultants, LLC; 🇺🇸 McAllen, Texas, United States

Metroplex Pulmonary and Sleep Center PA; 🇺🇸 McKinney, Texas, United States

Renovatio Clinical; 🇺🇸 The Woodlands, Texas, United States

Intermountain Healthcare; 🇺🇸 Murray, Utah, United States

University of Utah Health; 🇺🇸 Salt Lake City, Utah, United States

University of Virginia Health Systems; 🇺🇸 Charlottesville, Virginia, United States

Inova Fairfax Hospital; 🇺🇸 Falls Church, Virginia, United States

Pulmonary Associates of Richmond, Inc.; 🇺🇸 Richmond, Virginia, United States

University Hospital and UW Health Clinics; 🇺🇸 Madison, Wisconsin, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

CINME S.A. - Centro de Investigaciones Metabólicas; 🇦🇷 Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Instituto Ave Pulmo - Fundación enfisema; 🇦🇷 Mar del Plata, Buenos Aires, Argentina

Sanatorio Allende Cerro; 🇦🇷 Córdoba, Provincia De Córdoba, Argentina

Instituto Medico Río Cuarto; 🇦🇷 Rio Cuarto, Provincia De Córdoba, Argentina

Centro Médico INSARES; 🇦🇷 Mendoza, Provincia De Mendoza, Argentina

Centro Integral de Medicina Respiratoria (CIMER); 🇦🇷 San Miguel de Tucumán, Tucumán, Argentina

Investigaciones en Patologías Respiratorias; 🇦🇷 San Miguel de Tucumán, Tucumán, Argentina

Centro Médico Dra. De Salvo; 🇦🇷 Ciudad Autónoma de Buenos Aires, Argentina

Royal Prince Alfred Hospital; 🇦🇺 Camperdown, New South Wales, Australia

Macquarie University; 🇦🇺 Macquarie Park, New South Wales, Australia

Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia

Lung Research Qld; 🇦🇺 Chermside, Queensland, Australia

The Prince Charles Hospital; 🇦🇺 Chermside, Queensland, Australia

Mater Misericordiae Ltd; 🇦🇺 South Brisbane, Queensland, Australia

Alfred Health; 🇦🇺 Melbourne, Victoria, Australia

Ziekenhuis Aan de Stroom; 🇧🇪 Antwerpen, Belgium

Cliniques Universitaires Saint-Luc; 🇧🇪 Brussels, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium

CHR de la Citadelle; 🇧🇪 Liège, Belgium

St. Joseph's Healthcare Hamilton; 🇨🇦 Hamilton, Ontario, Canada

Centre d'investigation Clinique Mauricie; 🇨🇦 Trois-Rivières, Quebec, Canada

Institut Universitaire de Cardiologie et de Pneumologie de Quebec; 🇨🇦 Québec, Canada

Centro de Investigación del Maule SpA; 🇨🇱 Talca, Maule, Chile

CEC Centro de Estudios Clínicos; 🇨🇱 Santiago, Metropolitana, Chile

Instituto Nacional del tórax; 🇨🇱 Santiago, Región Metropolitana, Chile

Fundación Médica San Cristobal; 🇨🇱 Santiago, Región Metropolitana, Chile

Centro Respiratorio Integral Limitada; 🇨🇱 Quillota, Valparaiso, Chile

Aarhus University Hospital - Department of Respiratory Diseases and Allergy, Research Unit; 🇩🇰 Aarhus N, Denmark

Gentofte Hospital - Lungemedicinsk forskningsafdeling; 🇩🇰 Hellerup, Denmark

Odense University Hospital - Department of Respiratory Medicine; 🇩🇰 Odense C, Denmark

Hopital Nord AP-HM (Assistance Publique Hôpitaux De Marseille - Centre Hospitalier Régional de Marseille; 🇫🇷 Marseille, Bouches-du-Rhône, France

Hopital Larrey; 🇫🇷 Toulouse, Haute-Garonne, France

Barzilai Medical Center; 🇮🇱 Ashkelon, HaDarom, Israel

Hillel Yaffe Medical Center; 🇮🇱 Hadera, Haifa, Israel

Kaplan Medical Center; 🇮🇱 Rehovot, HaMerkaz, Israel

Shaare Zedek Medical Center; 🇮🇱 Jerusalem, Yerushalayim, Israel

Hadassah Medical Center - PPDS; 🇮🇱 Jerusalem, Yerushalayim, Israel

Azienda Ospedaliero Universitaria Di Modena Policlinico; 🇮🇹 Modena, Emilia-Romagna, Italy

A.O.U. Policlinico Vittorio Emanuele presidio "G.Rodolico"; 🇮🇹 Catania, Sicilia, Italy

Fondazione PTV Policlinico Tor Vergata; 🇮🇹 Roma, Italy

CHA Bundang Medical Center, CHA University; 🇰🇷 Seongnam-si, Gyeonggido, Korea, Republic of

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-Si, Gyeonggido, Korea, Republic of

Gachon University Gil Medical Center; 🇰🇷 Incheon, Incheon Gwang'yeogsi, Korea, Republic of

The Catholic University of Korea - Eunpyeong St. Mary's Hospital; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

SMG - SNU Boramae Medical Center; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Centro de Prevención y Rehabilitación de Enfermedades Pulmonares Crónicas (CEPREP); 🇲🇽 Monterrey, Nuevo León, Mexico

Unidad de Investigación Clínica en Medicina, S.C.; 🇲🇽 Monterrey, Nuevo León, Mexico

Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas; 🇲🇽 Ciudad de Mexico, Mexico

Zuyderland Medisch Centrum - Heerlen; 🇳🇱 Heerlen, Limburg, Netherlands

Erasmus MC -Dr. Molewaterplein 40; 🇳🇱 Rotterdam, Zuid-Holland, Netherlands

Waikato Hospital; 🇳🇿 Hamilton, Waikato, New Zealand

Canterbury Respiratory Research Group; 🇳🇿 Christchurch, New Zealand

Clinica Ricardo Palma; 🇵🇪 Lima, Peru

Hospital Central de la Fuerza Aérea del Perú; 🇵🇪 Lima, Peru

Hospital Universitario Central de Asturias; 🇪🇸 Oviedo, Asturias, Spain

Hospital Universitario Son Espases; 🇪🇸 Palma de Mallorca, Baleares, Spain

Hospital Universitario de Bellvitge; 🇪🇸 L´Hospitalet de LLobregat, Barcelona, Spain

Hospital Universitario Virgen de la Victoria; 🇪🇸 Malaga, Málaga, Spain

Hospital Universitario Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Hospital Universitario Virgen de Las Nieves; 🇪🇸 Granada, Spain

Hospital Universitario de La Princesa; 🇪🇸 Madrid, Spain

Far Eastern Memorial Hospital; 🇨🇳 New Taipei City, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan